Preclinical Evaluation of a Live Attenuated Chikungunya Vaccine

Abstract

Recently, Chikungunya virus (CHIKV) re-emerged in Africa and spread in the Indian subcontinent, South East Asia and Italy causing millions of cases of debilitating arthritis and fever in endemic ppulations and in travellers highlighting its growing impact on public health. Currently, there are no licensed vaccines to protect against CHIKV available. We developed a novel live attenuated CHIKV vaccine by using a rational attenuation mechanism that also prevents the infection of mosquito vectors. The subgenomic promoter was inactivated using 13 synonymous mutations and an internal ribosome entry site (IRES) from encephalomyocarditis virus was inserted into a cDNA CHIKV clone to drive translation of the structural protein genes. This new CHIKV vaccine strain was highly stable, safe, immunogenic and protective in mice. Current pre-clinical development efforts are aiming to test this vaccine in non-human primates and complete the Investigational New Drug (IND)-enabling studies necessary to begin human clinical testing. © 2012.